Early Data for HER2 Breast Ca Vax Promising

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

SAN FRANCISCO -- A cancer vaccine derived from HER2 protein demonstrated safety and preliminary evidence of activity in a randomized trial of patients with breast cancer.

No relapses occurred in patients with HER2-positive disease who completed the entire vaccine course after receiving standard treatment. After a 34-month median follow-up, vaccinated patients had a disease-free survival (DFS) of 88% as compared with 81% for patients who received an immunostimulant without the GP2 fragment of HER2 protein, reported Elizabeth A. Mittendorf, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston.

Exclusion of patients who recurred before completing immunization or who developed nonbreast malignancies yielded a DFS of 94% for vaccinated patients and 85% for the control group, they said at the Breast Cancer Symposium.

"The GP2 vaccine is safe and capable of stimulating an immune response," Mittendorf said. "In HER2-positive patients who complete the primary vaccination series after standard of care trastuzumab (Herceptin), there have been no recurrences. Combination immunotherapy with trastuzumab and the CD8 T-cell eliciting vaccine warrants further investigation."

Consisting of peptides derived from tumor-associated antigens and an immunoadjuvant, peptide cancer vaccines offer an attractive therapeutic strategy for several reasons. They are easy to construct and manufacture on a large scale, inexpensive, and off the shelf, meaning readily exportable into the community, Mittendorf explained.

Another HER2-derived vaccine (E75, nelipepimut-S) has progressed to phase III clinical evaluation. Evidence reported thus far has shown the vaccine is safe, can stimulate an antigen-specific immune response, and can offer a clinical benefit, Mittendorf continued.

The incidence of local and systemic toxicities (all grades) was similar between treatment groups, as a single grade 3 adverse event occurred among vaccinated patients. The data confirmed that the vaccine stimulated immune responses. The mean delayed-type hypersensitivity response in vaccinated patients increased by more than threefold from baseline and was more than double the post-immunization rate observed in patients who received GM-CSF alone (P<0.05).

Mittendorf and colleagues analyzed DFS in three ways: intention-to-treat (ITT), per treatment (ITT excluding patients who recurred during PVS and or developed nonbreast second malignancies), and a prespecified subgroup analysis limited to patients with the highest levels of HER2 expression (IHC 2-3+).

DFS favored the vaccine in all three analyses, but none of the differences achieved statistical significance:

"The current trial investigated sequential use of trastuzumab and the vaccine, and we observed two early recurrences and one second malignancy," Mittendorf said. "We hypothesize that concurrent use of vaccine with trastuzumab may address the early recurrences. A phase I trial of concurrent use showed the combination to be safe."

Clinical evaluation of GP2 is proceeding in a second phase II trial involving patients with high-risk HER2+ breast cancer. High risk is defined by failure to achieve a pathologic complete response with neoadjuvant chemotherapy and HER2-targeted treatment or patients who have upfront surgery and are node positive.

A surgical oncologist who moderated the session that included Mittendorf's presentation said the results are intriguing, but lack of a significant difference from the control group in all of the analyses warrants caution.

"This is a very exciting area and something we can look forward to," A. Marilyn Leitch, MD, of the University of Texas Southwestern Medical Center in Dallas told MedPage Today. "We still have patients who fail despite how well breast cancer patients do as a group. It is these types of developments that may help us deal with those patients."

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